Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes.

Affiliation

Ramanujam PL(#)(1), Mehrotra S(#)(1)(2), Kumar RP(3), Verma S(3), Deshpande G(4), Mishra RK(5), Galande S(6).
Author information:
(1)Department of Biology, Centre of Excellence in Epigenetics, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411008, India.
(2)Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Mumbai, India.
(3)Centre for Cellular and Molecular Biology, Hyderabad, India.
(4)Department of Molecular Biology, Princeton University, Princeton, NJ, 08540, USA.
(5)Centre for Cellular and Molecular Biology, Hyderabad, India. [Email]
(6)Department of Biology, Centre of Excellence in Epigenetics, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411008, India. [Email]
(#)Contributed equally

Abstract

Special AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive. Since Wnt/Wg signaling is conserved from invertebrates to humans, we investigated SATB1 functions in regulation of Wnt/Wg signaling by using mammalian cell-lines and Drosophila. Here, we present evidence that in mammalian cells, SATB1 interacts with Dishevelled, an upstream component of the Wnt/Wg pathway. Conversely, ectopic expression of full-length human SATB1 but not that of its N- or C-terminal domains in the eye imaginal discs and salivary glands of third instar Drosophila larvae increased the expression of Wnt/Wg pathway antagonists and suppressed phenotypes associated with activated Wnt/Wg pathway. These data argue that ectopically-provided SATB1 presumably modulates Wnt/Wg signaling by acting as negative regulator in Drosophila. Interestingly, comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. Collectively, these findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent.